Laboratoire de Glycochimie, des Antimicrobiens
et des Agroressources UMR 7378 CNRS


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Actualités et Publications

Development of C-type lectin-oriented surfaces for high avidity glycoconjugates: towards mimicking multivalent interactions on the cell surface,

Porkolab, V.; Pifferi, C.; Sutkeviciute, I.; Ordanini, S.; Taouai, M.; Thepaut, M.; Vivès, C.; Benazza, M.; Bernardi, A.; Renaudet, O.; Fieschi, F.

Org. Biomol. Chem. 2020.

Multivalent interactions between complex carbohydrates and oligomeric C-type lectins govern a wide range of immune responses. Up to date, standard SPR (surface plasmon resonance) competitive assays have largely been to evaluate binding properties from monosaccharide units (low affinity, mM) to multivalent elemental antagonists (moderate affinity, µM). Herein, we report typical case-studies of SPR competitive assays showing that they underestimate the potency of glycoclusters to inhibit the interaction between DC-SIGN and immobilized glycoconjugates. This paper describes the design and implementation of a SPR direct interaction over DC-SIGN oriented surfaces, extendable to other C-type lectin surfaces as such Langerin. This setup provides an overview of intrinsic avidity generation emanating simultaneously from multivalent glycoclusters and from DC-SIGN tetramers organized in nanoclusters at the cell membrane. To do so, covalent biospecific capture of DC-SIGN via StreptagII /StrepTactin interaction preserves tetrameric DC-SIGN, accessibility and topology of its active sites, that would have been dissociated using standard EDC-NHS procedure under acidic conditions. From the tested glycoclusters libraries, we demonstrated that the scaffold architecture, the valency and the glycomimetic-based ligand are crucial to reach nanomolar affinities for DC-SIGN. The glycocluster 3.D illustrates the tightest binding partner in this set for a DC-SIGN surface (KD= 18 nM). Moreover, the selectivity at monovalent scale of glycomimetic D can be easily analyzed at multivalent scale comparing its binding over different C-type lectin immobilized surfaces. This approach may give rise to novel insights into the multivalent binding mechanisms responsible for avidity and make a major contribution to the full characterization of the binding potency of promising specific and multivalent immodulators.

Amide Synthesis by Transamidation of Primary Carboxamides,

Kolympadi Marković, M.; Marković, D.; Laclef, S.


The amide functionality is one of the most important and widely used groups in nature and in medicinal and industrial chemistry. Because of its importance and as the actual synthetic methods suffer from major drawbacks, such as the use of a stoichiometric amount of an activating agent, epimerization and low atom economy, the development of new and efficient amide bond forming reactions is needed. A number of greener and more effective strategies have been studied and developed. The transamidation of primary amides is particularly attractive in terms of atom economy and as ammonia is the single byproduct. This review summarizes the advancements in metal-catalyzed and organocatalyzed transamidation methods. Lewis and Brønsted acid transamidation catalysts are reviewed as a separate group. The activation of primary amides by promoter, as well as catalyst- and promoter-free protocols, are also described. The proposed mechanisms and key intermediates of the depicted transamidation reactions are shown.

Cyclodextrin complexation studies as the first step for repurposing of chlorpromazine,

Wang, Z.; Landy, D.; Sizun, C.; Cézard, C.; Solgadi, A.; Przybylski, C.; de Chaisemartin, L.; Herfindal, L.; Barratt, G.; Legrand, F.-X.

Int. J. Pharm. 2020, 584, 119391.

The antipsychotic drug chlorpromazine (CPZ) has potential for the treatment of acute myeloid leukemia, if central nervous system side-effects resulting from its passage through the blood–brain barrier can be prevented. A robust drug delivery system for repurposed CPZ would be drug-in-cyclodextrin-in-liposome that would redirect the drug away from the brain while avoiding premature release in the circulation. As a first step, CPZ complexation with cyclodextrin (CD) has been studied. The stoichiometry, binding constant, enthalpy, and entropy of complex formation between CPZ and a panel of CDs was investigated by isothermal titration calorimetry (ITC). All the tested CDs were able to include CPZ, in the form of 1:1, 1:2 or a mixture of 1:1 and 1:2 complexes. In particular, a substituted γ-CD, sugammadex (the octasodium salt of octakis(6-deoxy-6-S-(2-carboxyethyl)-6-thio)cyclomaltooctaose), formed exclusively 1:2 complexes with an extremely high association constant of 6.37 × 109 M−2. Complexes were further characterized by heat capacity changes, one- and two-dimensional (ROESY) nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations. Finally, protection of CPZ against photodegradation by CDs was assessed. This was accelerated rather than reduced by complexation with CD. Altogether these results provide a molecular basis for the use of CD in delayed release formulations for CPZ.

New biobased-zwitterionic ionic liquids: efficiency and biocompatibility for the development of sustainable biorefinery processes,

Huet, G.; Araya-Farias, M.; Alayoubi, R.; Laclef, S.; Bouvier, B.; Gosselin, I.; Cézard, C.; Roulard, R.; Courty, M.; Hadad, C.; Husson, E.; Sarazin, C.; Nguyen Van Nhien, A.

Green Chem. 2020, 22, 2935-2946.

A new family of biobased-zwitterionic ionic liquids (ZILs) have been synthesized starting from the renewable resource l-histidine natural amino acid and varying the lengths of the alkyl chains. These ZIL derivatives were firstly studied for their biocompatibility with different microorganisms including bacteria, molds and yeast. The obtained MIC values indicated that all the microorganisms were 5 to 25 times more tolerant to ZIL derivatives than the robust 1-ethyl-3-methylimidazolium acetate [C2mim][OAc] used as a reference. Modeling studies also revealed that the presence of the cation and the anion on the same skeleton together with the length of the N-alkyl chain would govern the biocompatibility of these neoteric solvents. Among the different synthesized ZILs, the N,N′-diethyl derivative has been demonstrated to be a suitable eco-alternative to the classically used [C2mim][OAc] for efficient pretreatment of harwood sawdust leading to a significant improvement of enzymatic saccharification. In addition, with up to a 5% w/v concentration in the culture medium, ZILs did not induce deleterious effects on fermentative yeast growth nor ethanol production.

Marine Natural Products with High Anticancer Activities,

Dario, M.; Karlo, W.; Nela, M.; Sylvain, L.; Maris, T.; Maria, K.; Gabriela, A.; Dean, M.

Curr. Med. Chem. 2020, 27, 1-63.

This review covers recent literature from 2012-2019 concerning 170 marine natural products and their semisynthetic analogues with strong anticancer biological activities. Reports that shed light on cellular and molecular mechanisms and biological functions of these compounds, thus advancing the understanding in cancer biology are also included. Biosynthetic studies and total syntheses, which have provided access to derivatives and have contributed to the proper structure or stereochemistry elucidation or revision are mentioned. The natural compounds isolated from marine organisms are divided into nine groups, namely: alkaloids, sterols and steroids, glycosides, terpenes and terpenoids, macrolides, polypeptides, quinones, phenols and polyphenols, and miscellaneous products. An emphasis is placed on several drugs originating from marine natural products that have already been marketed or are currently in clinical trials.

Production of Oligosaccharides from Agrofood Wastes,

Cano, M. E.; García-Martin, A.; Comendador Morales, P.; Wojtusik, M.; Santos, V. E.; Kovensky, J.; Ladero, M.

Fermentation 2020, 6, 31.

The development of biorefinery processes to platform chemicals for most lignocellulosic substrates, results in side processes to intermediates such as oligosaccharides. Agrofood wastes are most amenable to produce such intermediates, in particular, cellooligo-saccharides (COS), pectooligosaccharides (POS), xylooligosaccharides (XOS) and other less abundant oligomers containing mannose, arabinose, galactose and several sugar acids. These compounds show a remarkable bioactivity as prebiotics, elicitors in plants, food complements, healthy coadyuvants in certain therapies and more. They are medium to high added-value compounds with an increasing impact in the pharmaceutical, nutraceutical, cosmetic and food industries. This review is focused on the main production processes: autohydrolysis, acid and basic catalysis and enzymatic saccharification. Autohydrolysis of food residues at 160–190 °C leads to oligomer yields in the 0.06–0.3 g/g dry solid range, while acid hydrolysis of pectin (80–120 °C) or cellulose (45–180 °C) yields up to 0.7 g/g dry polymer. Enzymatic hydrolysis at 40–50 °C of pure polysaccharides results in 0.06–0.35 g/g dry solid (DS), with values in the range 0.08–0.2 g/g DS for original food residues.

Laboratoire de Glycochimie, des Antimicrobiens et des Agroressources
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